In this second Major Observation, Dr. Egawa discussed a paper by Sridharan et al, which focused on prostate cancer oligometastatic disease treated with radiotherapy as part of the TROG 03.04 RADAR study. In this study, patients with pT2aN0M0 intermediate localized disease OR pT2-4 any grade or PSA treated with radiotherapy. They randomized 2273 patients, and PCSM was the primary endpoint. There were 4 arms to the trial – two arms received ADT alone prior to RT, while 2 arms received ADT/Zoledronic acid. Two of the arms received no adjuvant therapy, while 1 arm received 12 months ADT and 1 arm received 12 months ADT/zoledronic acid.
Dr. Egawa found this paper interesting due to number of bone metastatic events during follow-up. They stratified PCSM by number of bone metastases and found a strong correlation. More importantly, in the patients that develop castration resistant prostate cancer, there is a period of time where they are non-metastatic. However, there is then a rapid separation of cohorts stratified by number of bone metastases and PCSM – what is the cause of this distinct natural history? What predisposes some to multiple bone mets and worse prognosis while others remain more indolent?
A paper by Smith et al (Cancer 2011), patients with nmCRPC have heterogeneous natural history. Baseline PSA > 13.1 and PSAV were important predictors of bone-metastases free survival and overall survival.
However, non-metastatic CRPC (cM0 CRPC) is a misleading term. There is likely evidence of metastases that conventional imaging cannot yet determine. While there are novel imaging technologies detecting disease at smaller volumes, further work needs to be done in this field to help identify the bad actors.
He briefly reviewing his institutional experience with nmCRPC (cM0 CRPC). Patients with cM0 CRPC had obbiously better survival that mCRPC, likely due to lead time bias. PSAV and PSADT for cM0 CRPC patients was suggesting of aggressive disease – PSAV 1.7 ng/mL/month, PSADT 2.1.
As with all areas of urologic oncology, this begs the question of risk stratification? How can we better identify those patients? Can we treat more aggressively those patients at risk?
1. Sridharan S, et al. Oligometastatic bone disease in prostate cancer patients treated on the TROG 03.04 RADAR trial. Radiother Oncol. 2016 Oct;121(1):98-102. doi: 10.1016/j.radonc.2016.07.021. Epub 2016 Aug 12.